Esophageal cancer is a leading cause of death from cancer worldwide. The two principal types of esophageal cancer are squamous cell carcinoma and adenocarcinoma. Both are relatively uncommon in the U.S., comprising approximately 1% of all cancers. However, the incidence of adenocarcinoma is rising at a rapid rate. According to a report from American Cancer Society, 12,300 new cases and 12,100 deaths were reported in 2000, and the corresponding numbers for 2009 are 16,470 and 14,530, respectively. The 5-year survival rates for localized and all stages combined are 34% and 17%, respectively. Moreover, there is no currently reliable method for early detection or for the prediction of treatment outcome.
Barrett's esophagus (BE), high-grade dysplasia (HGD), and invasive cancer are thought to comprise a multi-step process in the development of esophageal adenocarcinoma (EAC). HGD has been considered as the immediate precursor of invasive adenocarcinoma. Since most patients with HGD are usually bearing or developing cancer, HGD has been regarded as a marker of progression to carcinoma. However, no intervention currently exists that prevents the progression of BE or HGD to esophageal cancer. The traditional methods for diagnosing esophageal cancer include endoscopy and barium swallow, but the poor specificity and sensitivity of these methods results in their detection only at an advanced stage. Recently, prognostic and predictive protein and genetic markers have been introduced to aid in the diagnosis of esophageal cancer. However, biomarkers effective at a potentially curative stage are lacking.
Metabotomics (or metabolite profiling) is the study of concentrations and fluxes of low molecular weight metabolites present in biofluids or tissues that provide detailed information on biological systems and their current status. The field of metabolomics emphasizes the multiplexed analysis of known and unknown metabolites in complex biological matrices such as pathological and normal tissue and biological fluids (“biofluids”). In various forms of metabolomics, the low molecular weight metabolites are detected and quantified by techniques such as nuclear magnetic resonance (NMR) spectrometry, gas chromatography-mass spectrometry (GC-MS), liquid chromatography-mass spectrometry (LC-MS), and capillary electrophoresis-mass spectrometry. Metabolomics aims to improve the molecular level understanding of metabolic pathways associated with many diseases or other biological states in a system biology approach.
Early diagnostic methods that offer high sensitivity and specificity for detecting esophageal cancer are in great demand. We have found that tests based on metabolic profiles that use a combination of the metabolic biomarkers that were identified using NMR with the metabolic biomarkers that were identified using LC-MS have improved sensitivity and selectivity compared to tests based on metabolic biomarkers that were identified either method alone.